Identification and characterization of a new oncogene derived from the regulatory subunit of phosphoinositide 3-kinase.
p85/p110 phosphoinositide 3-kinase (PI3K) is a heterodimer composed of a p85-regulatory and a p110-catalytic subunit, which is involved in a variety of cellular responses including cytoskeletal organization, cell survival and proliferation. We describe here the cloning and characterization of p65-PI3K, a mutant of the regulatory subunit of PI3K, which includes the initial 571 residues of the wild type p85alpha-protein linked to a region conserved in the eph tyrosine kinase receptor family. We demonstrate that this mutation, obtained from a transformed cell, unlike previously engineered mutations of the regulatory subunit, induces the constitutive activation of PI3K and contributes to cellular transformation. This report links the PI3K enzyme to mammalian tumor development for the first time.
Jimenez
C
C
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autónoma de Madrid, Cantoblanco, Madrid E-28049, Spain.
Jones
D R
DR
Rodríguez-Viciana
P
P
Gonzalez-García
A
A
Leonardo
E
E
Wennström
S
S
von Kobbe
C
C
Toran
J L
JL
R-Borlado
L
L
Calvo
V
V
Copin
S G
SG
Albar
J P
JP
Gaspar
M L
ML
Diez
E
E
Marcos
M A
MA
Downward
J
J
Martinez-A
C
C
Mérida
I
I
Carrera
A C
AC
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002135:Calcium-Binding Proteins; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D003001:Cloning, Molecular; D004790:Enzyme Induction / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000502:physiology; D009857:Oncogenes / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D010716:Phosphatidylinositols / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins; D050863:Synaptotagmin I; D050857:Synaptotagmins